Network pharmacology of Epilobium angustifolium metabolites in relation to in vitro analyses of its extracts

Epilobium angustifolium L. is a perennial herbaceous plant known for various therapeutic properties, however its biological activity is not fully explored. In this study, we examined antioxidant activities of extracts of different polarity (n-hexane, ethyl acetate and 70 % ethanol in water) and their potential to inhibit amylase, glucosidase, tyrosinase, acetylcholinesterase and butyrylcholinesterase, as well as cytotoxic effects. Moreover, phytochemical analysis performed with liquid chromatography-mass spectrometry (LC-ESI-QTOF-MS) revealed the presence of hydrolysable tannins (gallotannins and ellagitannins), flavonoids, phenolic acids derivatives and esters of saccharides, triterpenoids and lipids. The aqueous-ethanolic extract exhibited the best radical scavenging and reducing abilities. The identified compounds in the extracts were subjected to Disease Ontology enrichment analysis and screening of potential targets, which identified significant associations with colon carcinoma and gastric adenocarcinoma. The predicted cytotoxicity was checked against cancerous and non-cancerous cell lines. The E. angustifolium aqueous-ethanolic extract showed weak cytotoxicity on non-cancerous monkey kidney fibroblasts (VERO cells) and moderate cytotoxicity against cancer-derived cells (malignant melanoma, human gastric adenocarcinoma, human hypopharyngeal squamous cell carcinoma, human colon cancer), with the highest toxicity and cytotoxic selectivity observed for hypopharyngeal (CC50 = 37.52 μg/mL, SI = 6.39) and colon (CC50 = 37.27 μg/mL, SI = 6.43) cancer-derived cells. Key drug targets were identified using CTD, STRING, GeneCards, and DisGeNET databases, followed by protein-protein interaction network analysis. Molecular docking using AutoDock Vina revealed that compounds gemin D and hamamelitannin demonstrated strong binding affinities with cancer-related proteins. These findings revealed the potential of indicated molecules as anti-proliferative agents and suggest the need for further research to optimize their efficacy.